Вопросы вирусологии. 2019; 64: 281-290
Анализ полиморфизма белка Nef вариантов ВИЧ-1 (Human immunodeficiency virus-1, Lentivirus, Orthoretrovirinae, Retroviridae), циркулирующих в странах бывшего СССР
https://doi.org/10.36233/0507-4088-2019-64-6-281-290Аннотация
Цели и задачи. Основной целью работы был анализ особенностей белка Nef варианта А6 ВИЧ-1, доминирующего
в странах бывшего СССР. Задачей работы послужил сравнительный анализ естественных полиморфизмов в генe nef ВИЧ-1 суб-субтипов А6 и А1 и субтипа B.
Материал и методы. Материалом для работы послужили последовательности генома ВИЧ-1, полученные в ходе предшествующей работы лаборатории, а также референс-последовательности из GenBank. В работе использованы методы секвенирования по Сэнгеру и секвенирования нового поколения, а также методы биоинформационного анализа.
Результаты и обсуждение. Продемонстрированы различия в частоте встречаемости естественных полиморфизмов белка Nef (A32P, E38D, I43V, A54D, Q104K, H116N, Y120F, Y143F, V168M, H192T, V194R, R35Q, D108E, Y135F, E155K, E182M, R184K и F191L), некоторые из которых являются характеристическими мутациями для варианта А6.
Заключение. Обнаружены характеристические замены в составе Nef, потенциально способные ослаблять репликативные свойства варианта А6 ВИЧ-1.
Список литературы
1. Saksena N.K., Ge Y.C., Wang B., Xiang S.H., Dwyer D.E., Randle C., et al. An HIV-1 infected long-term non-progressor (LTNP): molecular analysis of HIV-1 strains in the vpr and nef genes. Ann. Acad. Med. Singapore. 1996; 25(6): 848-54.
2. Wang B. Viral factors in non-progression. Front. Immunol. 2013; 4: 355. Doi: https://doi.org/10.3389/fimmu.2013.00355
3. Arhel N.J., Kirchhoff F. Implications of Nef: host cell interactions in viral persistence and progression to AIDS. Curr. Top. Microbiol. Immunol. 2009; 339: 147-75. Doi: https://doi.org/10.1007/978-3-642-02175-6_8
4. Basmaciogullari S., Pizzato M. The activity of Nef on HIV-1 infectivity. Front. Microbiol. 2014; 5: 232. Doi: https://doi.org/10.3389/fmicb.2014.00232
5. Pereira E.A., daSilva L.L. HIV-1 Nef: Taking Control of Protein Trafficking. Traffic. 2016; 17(9): 976-96. Doi: https://doi.org/10.1111/tra.12412
6. Jager S., Cimermancic P., Gulbahce N., Johnson J.R., McGovern K.E., Clarke S.C., et al. Global landscape of HIV-human protein complexes. Nature. 2011; 481(7381): 365-70. Doi: https://doi.org/10.1038/nature10719
7. Dekaban G.A., Dikeakos J.D. HIV-I Nef inhibitors: a novel class of HIV-specific immune adjuvants in support of a cure. AIDS Res. Ther. 2017; 14(1): 53. Doi: https://doi.org/10.1186/s12981-017-0175-6
8. Van den Broeke C., Radu M., Chernoff J., Favoreel H.W. An emerging role for p21-activated kinases (Paks) in viral infections. Trends Cell Biol. 2010; 20(3): 160-9. Doi: https://doi.org/10.1016/j.tcb.2009.12.005
9. Stolp B., Fackler O.T. How HIV takes advantage of the cytoskeleton in entry and replication. Viruses. 2011; 3(4): 293-311. Doi: https://doi.org/10.3390/v3040293
10. Sourisseau M., Sol-Foulon N., Porrot F., Blanchet F., Schwartz O. Inefficient human immunodeficiency virus replication in mobile lymphocytes. J. Virol. 2007; 81(2):1000-12. Doi: https://doi.org/10.1128/JVI.01629-06
11. Vermeire J., Vanbillemont G., Witkowski W.,Verhasselt B. The Nefinfectivity enigma: mechanisms of enhanced lentiviral infection. Curr. HIV Res. 2011; 9(7): 474-89. Doi: https://doi.org/10.2174/157016211798842099
12. Rosa A., Chande A., Ziglio S., De Sanctis V., Bertorelli R., Goh S.L., et al. HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation. Nature. 2015; 526(7572): 212-7. Doi: https://doi.org/10.1038/nature15399
13. Lama J. The physiological relevance of CD4 receptor down-modulation during HIV infection. Curr. HIV Res. 2003; 1(2): 167-84. Doi: https://doi.org/10.2174/1570162033485276
14. Toyoda M., Ogata Y., Mahiti M., Maeda Y., Kuang X.T., Miura T., et al. Differential Ability of Primary HIV-1 Nef Isolates To Downregulate HIV-1 Entry Receptors. J. Virol. 2015; 89(18): 9639-52. Doi: https://doi.org/10.1128/JVI.01548-15
15. Dikeakos J.D., Thomas L., Kwon G., Elferich J., Shinde U., Thomas G. An interdomain binding site on HIV-1 Nef interacts with PACS-1 and PACS-2 on endosomes to down-regulate MHC-I. Mol. Biol. Cell. 2012; 23(11): 2184-97. Doi: https://doi.org/10.1091/mbc.E11-11-0928
16. Lewis M.J., Lee P., Ng H.L.,Yang O.O. Immune selection in vitro reveals human immunodeficiency virus type 1 Nef sequence motifs important for its immune evasion function in vivo. J. Virol. 2012; 86(13): 7126-35. Doi: https://doi.org/10.1128/JVI.00878-12
17. Olivetta E., Arenaccio C., Manfredi F., Anticoli S., Federico M. The Contribution of Extracellular Nef to HIV-Induced Pathogenesis. Curr. Drug Targets. 2016; 17(1): 46-53. Doi: https://doi.org/10.2174/1389450116666151001110126
18. Lamers S.L., Poon A.F., McGrath M.S. HIV-1 nef protein structures associated with brain infection and dementia pathogenesis. PLoS One. 2011; 6(2): e16659. Doi: https://doi.org/10.1371/journal.pone.0016659
19. Anand A.R., Rachel G., Parthasarathy D. HIV Proteins and Endothelial Dysfunction: Implications in Cardiovascular Disease. Front. Cardiovasc. Med. 2018; 5: 185. Doi: https://doi.org/10.3389/fcvm.2018.00185
20. Almodovar S., Knight R., Allshouse A.A., Roemer S., Lozupone C., McDonald D., et al. Human Immunodeficiency Virus nef signature sequences are associated with pulmonary hypertension. AIDS Res. Hum. Retroviruses. 2012; 28(6): 607-18. Doi: https://doi.org/10.1089/AID.2011.0021
21. Emert-Sedlak L.A., Loughran H.M., Shi H., Kulp J.L., Shu S.T., Zhao J., et al. Synthesis and evaluation of orally active small molecule HIV-1 Nef antagonists. Bioorg. Med. Chem. Lett. 2016; 26(5): 1480-4. Doi: https://doi.org/10.1016/j.bmcl.2016.01.043
22. Hunegnaw R., Vassylyeva M., Dubrovsky L., Pushkarsky T., Sviridov D., Anashkina A.A., et al. Interaction Between HIV-1 Nef and Calnexin: From Modeling to Small Molecule Inhibitors Reversing HIV-Induced Lipid Accumulation. Arterioscler. Thromb. Vasc. Biol. 2016; 36(9): 1758-71. Doi: https://doi.org/10.1161/ATVBAHA.116.307997
23. Corro G., Rocco C.A., De Candia C., Catano G., Turk G., Mangano A., et al. Genetic and functional analysis of HIV type 1 nef gene derived from long-term nonprogressor children: association of attenuated variants with slow progression to pediatric AIDS. AIDS Res. Hum. Retroviruses. 2012; 28(12): 1617-26. Doi: https://doi.org/10.1089/AID.2012.0020
24. Foster J.L., Denial S.J., Temple B.R., Garcia J.V. Mechanisms of HIV-1 Nef function and intracellular signaling. J. Neuroimmune Pharmacol. 2011; 6(2): 230-46. Doi: https://doi.org/10.1007/s11481-011-9262-y
25. O’Neill E., Kuo L.S., Krisko J.F., Tomchick D.R., Garcia J.V., Foster J.L. Dynamic evolution of the human immunodeficiency virus type 1 pathogenic factor, Nef. J. Virol. 2006; 80(3): 1311-20. Doi: https://doi.org/10.1128/JVI.80.3.1311-1320.2006
26. Usmani S.M., Murooka T.T., Deruaz M., Koh W.H., Sharaf R.R., Di Pilato M., et al. HIV-1 Balances the Fitness Costs and Benefits of Disrupting the Host Cell Actin Cytoskeleton Early after Mucosal Transmission. Cell. Host Microbe. 2019; 25(1): 73-86. Doi: https://doi.org/10.1016/j.chom.2018.12.008
27. Kumar S., Stecher G.,Tamura K. MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets. Mol. Biol. Evol. 2016; 33(7): 1870-4. Doi: https://doi.org/10.1093/molbev/msw054
28. Tamura K., Stecher G., Peterson D., Filipski A., Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0. Mol. Biol. Evol. 2013; 30(12): 2725-9. Doi: https://doi.org/10.1093/molbev/mst197
29. Golosova O., Henderson R., Vaskin Y., Gabrielian A., Grekhov G., Nagarajan V., et al. Unipro UGENE NGS pipelines and components for variant calling, RNA-seq and ChIP-seq data analyses. PeerJ. 2014; 2: e644. Doi: https://doi.org/10.7717/peerj.644
30. Nguyen L.T., Schmidt H.A., von Haeseler A., Minh B.Q. IQTREE: A Fast and Effective Stochastic Algorithm for Estimating Maximum-Likelihood Phylogenies. Mol. Biol. Evol. 2015; 32(1): 268-74. Doi: https://doi.org/10.1093/molbev/msu300
31. Ratner L., Haseltine W., Patarca R., Livak K.J., Starcich B., Josephs S.F., et al. Complete Nucleotide-Sequence of the AIDS Virus, HTLV-III. Nature. 1985; 313(6000): 277-84. Doi: https://doi.org/10.1038/313277a0
Problems of Virology. 2019; 64: 281-290
Analysis of HIV-1 (Human immunodeficiency virus-1, Lentivirus, Orthoretrovirinae, Retroviridae) Nef protein polymorphism of variants circulating in the former USSR countries
https://doi.org/10.36233/0507-4088-2019-64-6-281-290Abstract
Goals and tasks. The main goal of the work was to analyze the characteristics of Nef protein of HIV-1 variant A6, which dominates in the countries of the former USSR. The objective of the work was a comparative analysis of natural polymorphisms in the nef gene of HIV-1 sub-subtypes A6 and A1 and subtype B.
Material and methods. The sequences of the HIV-1 genome obtained during the previous work of the laboratory were used, as well as the reference sequence from GenBank. In this work, Sanger sequencing and new generation sequencing methods, as well as bioinformation analysis methods were used.
Results and discussion. The existence of noticeable differences in the prevalence of Nef natural polymorphisms (A32P, E38D, I43V, A54D, Q104K, H116N, Y120F, Y143F, V168M, H192T, V194R, R35Q, D108E, Y135F, E155K, E182M, R184K and F191L), some of which are characteristic mutations for variant A6, was shown. Conclusion. Characteristic substitutions were found in the Nef structure, potentially capable of weakening the replicative properties of HIV-1 variant A6.
References
1. Saksena N.K., Ge Y.C., Wang B., Xiang S.H., Dwyer D.E., Randle C., et al. An HIV-1 infected long-term non-progressor (LTNP): molecular analysis of HIV-1 strains in the vpr and nef genes. Ann. Acad. Med. Singapore. 1996; 25(6): 848-54.
2. Wang B. Viral factors in non-progression. Front. Immunol. 2013; 4: 355. Doi: https://doi.org/10.3389/fimmu.2013.00355
3. Arhel N.J., Kirchhoff F. Implications of Nef: host cell interactions in viral persistence and progression to AIDS. Curr. Top. Microbiol. Immunol. 2009; 339: 147-75. Doi: https://doi.org/10.1007/978-3-642-02175-6_8
4. Basmaciogullari S., Pizzato M. The activity of Nef on HIV-1 infectivity. Front. Microbiol. 2014; 5: 232. Doi: https://doi.org/10.3389/fmicb.2014.00232
5. Pereira E.A., daSilva L.L. HIV-1 Nef: Taking Control of Protein Trafficking. Traffic. 2016; 17(9): 976-96. Doi: https://doi.org/10.1111/tra.12412
6. Jager S., Cimermancic P., Gulbahce N., Johnson J.R., McGovern K.E., Clarke S.C., et al. Global landscape of HIV-human protein complexes. Nature. 2011; 481(7381): 365-70. Doi: https://doi.org/10.1038/nature10719
7. Dekaban G.A., Dikeakos J.D. HIV-I Nef inhibitors: a novel class of HIV-specific immune adjuvants in support of a cure. AIDS Res. Ther. 2017; 14(1): 53. Doi: https://doi.org/10.1186/s12981-017-0175-6
8. Van den Broeke C., Radu M., Chernoff J., Favoreel H.W. An emerging role for p21-activated kinases (Paks) in viral infections. Trends Cell Biol. 2010; 20(3): 160-9. Doi: https://doi.org/10.1016/j.tcb.2009.12.005
9. Stolp B., Fackler O.T. How HIV takes advantage of the cytoskeleton in entry and replication. Viruses. 2011; 3(4): 293-311. Doi: https://doi.org/10.3390/v3040293
10. Sourisseau M., Sol-Foulon N., Porrot F., Blanchet F., Schwartz O. Inefficient human immunodeficiency virus replication in mobile lymphocytes. J. Virol. 2007; 81(2):1000-12. Doi: https://doi.org/10.1128/JVI.01629-06
11. Vermeire J., Vanbillemont G., Witkowski W.,Verhasselt B. The Nefinfectivity enigma: mechanisms of enhanced lentiviral infection. Curr. HIV Res. 2011; 9(7): 474-89. Doi: https://doi.org/10.2174/157016211798842099
12. Rosa A., Chande A., Ziglio S., De Sanctis V., Bertorelli R., Goh S.L., et al. HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation. Nature. 2015; 526(7572): 212-7. Doi: https://doi.org/10.1038/nature15399
13. Lama J. The physiological relevance of CD4 receptor down-modulation during HIV infection. Curr. HIV Res. 2003; 1(2): 167-84. Doi: https://doi.org/10.2174/1570162033485276
14. Toyoda M., Ogata Y., Mahiti M., Maeda Y., Kuang X.T., Miura T., et al. Differential Ability of Primary HIV-1 Nef Isolates To Downregulate HIV-1 Entry Receptors. J. Virol. 2015; 89(18): 9639-52. Doi: https://doi.org/10.1128/JVI.01548-15
15. Dikeakos J.D., Thomas L., Kwon G., Elferich J., Shinde U., Thomas G. An interdomain binding site on HIV-1 Nef interacts with PACS-1 and PACS-2 on endosomes to down-regulate MHC-I. Mol. Biol. Cell. 2012; 23(11): 2184-97. Doi: https://doi.org/10.1091/mbc.E11-11-0928
16. Lewis M.J., Lee P., Ng H.L.,Yang O.O. Immune selection in vitro reveals human immunodeficiency virus type 1 Nef sequence motifs important for its immune evasion function in vivo. J. Virol. 2012; 86(13): 7126-35. Doi: https://doi.org/10.1128/JVI.00878-12
17. Olivetta E., Arenaccio C., Manfredi F., Anticoli S., Federico M. The Contribution of Extracellular Nef to HIV-Induced Pathogenesis. Curr. Drug Targets. 2016; 17(1): 46-53. Doi: https://doi.org/10.2174/1389450116666151001110126
18. Lamers S.L., Poon A.F., McGrath M.S. HIV-1 nef protein structures associated with brain infection and dementia pathogenesis. PLoS One. 2011; 6(2): e16659. Doi: https://doi.org/10.1371/journal.pone.0016659
19. Anand A.R., Rachel G., Parthasarathy D. HIV Proteins and Endothelial Dysfunction: Implications in Cardiovascular Disease. Front. Cardiovasc. Med. 2018; 5: 185. Doi: https://doi.org/10.3389/fcvm.2018.00185
20. Almodovar S., Knight R., Allshouse A.A., Roemer S., Lozupone C., McDonald D., et al. Human Immunodeficiency Virus nef signature sequences are associated with pulmonary hypertension. AIDS Res. Hum. Retroviruses. 2012; 28(6): 607-18. Doi: https://doi.org/10.1089/AID.2011.0021
21. Emert-Sedlak L.A., Loughran H.M., Shi H., Kulp J.L., Shu S.T., Zhao J., et al. Synthesis and evaluation of orally active small molecule HIV-1 Nef antagonists. Bioorg. Med. Chem. Lett. 2016; 26(5): 1480-4. Doi: https://doi.org/10.1016/j.bmcl.2016.01.043
22. Hunegnaw R., Vassylyeva M., Dubrovsky L., Pushkarsky T., Sviridov D., Anashkina A.A., et al. Interaction Between HIV-1 Nef and Calnexin: From Modeling to Small Molecule Inhibitors Reversing HIV-Induced Lipid Accumulation. Arterioscler. Thromb. Vasc. Biol. 2016; 36(9): 1758-71. Doi: https://doi.org/10.1161/ATVBAHA.116.307997
23. Corro G., Rocco C.A., De Candia C., Catano G., Turk G., Mangano A., et al. Genetic and functional analysis of HIV type 1 nef gene derived from long-term nonprogressor children: association of attenuated variants with slow progression to pediatric AIDS. AIDS Res. Hum. Retroviruses. 2012; 28(12): 1617-26. Doi: https://doi.org/10.1089/AID.2012.0020
24. Foster J.L., Denial S.J., Temple B.R., Garcia J.V. Mechanisms of HIV-1 Nef function and intracellular signaling. J. Neuroimmune Pharmacol. 2011; 6(2): 230-46. Doi: https://doi.org/10.1007/s11481-011-9262-y
25. O’Neill E., Kuo L.S., Krisko J.F., Tomchick D.R., Garcia J.V., Foster J.L. Dynamic evolution of the human immunodeficiency virus type 1 pathogenic factor, Nef. J. Virol. 2006; 80(3): 1311-20. Doi: https://doi.org/10.1128/JVI.80.3.1311-1320.2006
26. Usmani S.M., Murooka T.T., Deruaz M., Koh W.H., Sharaf R.R., Di Pilato M., et al. HIV-1 Balances the Fitness Costs and Benefits of Disrupting the Host Cell Actin Cytoskeleton Early after Mucosal Transmission. Cell. Host Microbe. 2019; 25(1): 73-86. Doi: https://doi.org/10.1016/j.chom.2018.12.008
27. Kumar S., Stecher G.,Tamura K. MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets. Mol. Biol. Evol. 2016; 33(7): 1870-4. Doi: https://doi.org/10.1093/molbev/msw054
28. Tamura K., Stecher G., Peterson D., Filipski A., Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0. Mol. Biol. Evol. 2013; 30(12): 2725-9. Doi: https://doi.org/10.1093/molbev/mst197
29. Golosova O., Henderson R., Vaskin Y., Gabrielian A., Grekhov G., Nagarajan V., et al. Unipro UGENE NGS pipelines and components for variant calling, RNA-seq and ChIP-seq data analyses. PeerJ. 2014; 2: e644. Doi: https://doi.org/10.7717/peerj.644
30. Nguyen L.T., Schmidt H.A., von Haeseler A., Minh B.Q. IQTREE: A Fast and Effective Stochastic Algorithm for Estimating Maximum-Likelihood Phylogenies. Mol. Biol. Evol. 2015; 32(1): 268-74. Doi: https://doi.org/10.1093/molbev/msu300
31. Ratner L., Haseltine W., Patarca R., Livak K.J., Starcich B., Josephs S.F., et al. Complete Nucleotide-Sequence of the AIDS Virus, HTLV-III. Nature. 1985; 313(6000): 277-84. Doi: https://doi.org/10.1038/313277a0
